This is an initial application for a K08 for Jesse Nussbaum, MD at the University of California, San Francisco. Dr. Nussbaum has completed fellowship training in Infectious Diseases and now seeks funding and protected time for training to develop an independent physician scientist career in host-parasite interactions. The candidate has excelled in basic and clinical research, as evidenced by publication of his work at each stage of his training. He most recently joined the laboratory of Dr. Richard Locksley to gain expertise in the use of model organisms to study the field of host immunity. This proposal has two training goals: (1) The career development plan describes the scientific fields (e.g. immunology, parasitology, microscopy) and professional competencies (e.g. presentation, grant-writing) that Dr. Nussbaum will need to master in order to achieve scientific independence. The plan details benchmarks for coursework, seminars, and mentoring. (2) Dr. Nussbaum's research strategy addresses a clinically and scientifically important subject. Understanding the conserved signals that initiate and maintain immune responses to helminths will answer crucial questions about co-evolved host-pathogen interactions and enable therapies that improve life in the developing world. This research plan is both innovative and achievable. It uses well-established models and existing mouse strains to define novel interactions between T helper cells and newly discovered innate lymphocytes. The candidate's specific aims are to define (1) the dynamic properties of these cell-cell interactions, (2) the relative contribution of these cell to memory immune responses, and (3) the role of hormonal signals in lymphocyte activation. These aims build on Dr. Nussbaum's previous work but also incorporate new techniques that require further training. Dr. Nussbaum has assembled a mentoring committee, comprised of primary mentor, Dr. Richard Locksley, Professor of Medicine and Microbiology and Immunology and physician-scientist expert in infectious diseases and immunology; Dr. Matthew Krummel, expert in advanced imaging of the immune system; Dr. James McKerrow, expert in host-parasite biology and drug discovery; and Dr. Mark Anderson, expert in T cell development and Director of the UCSF Medical Scientist Training Program. The committee is structured to provide complementary scientific and career perspectives, and its members are close collaborators. Dr. Nussbaum has the full support of the Division of Infectious Diseases where he will be an Assistant Professor, a position that is not contingent upon receiving this award. UCSF's institutional environment provides well-resourced facilities and a strong track record of training early-stage physician scientists. The Department of Medicine and Department of Immunology and Microbiology will assist the candidate through access to diverse faculty collaborations and protected time (at least 75%) devoted to his research activities. This proposal forms a basis for Dr. Nussbaum's further career development, ensuring training and original contributions to science that will allow him to compete for funding of his independent research program.